Rapsyn regulation of ACh receptor function

Rapsyn 对 ACh 受体功能的调节

• 批准号: 7489559
• 负责人: Mark A Verdecia
• 金额: $ 0.55万
• 依托单位: OREGON HEALTH & SCIENCE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7489559
• 关键词: Rapsyn; regulation; ACh; receptor; function

DESCRIPTION (provided by applicant): My main objective is to determine how rapsyn directs the increase in AChR density at the neuromuscular junction (NMJ). Severe effects on development and health result when the NMJ becomes impaired. The autoimmune disease myasthenia gravis (MG) and its genetic counterpart, congenital myasthenic syndrome (CMS), which result in muscle weakness and fatigue, are both caused by defects in specific components of the NMJ, including rapsyn in many cases. To date, analysis of rapsyn has been relegated to heterologous expression systems and ectopic NMJs in tissue culture. These studies have yet to clarify rapsyn's function and have only served to add to the controversy regarding its mode of action. Findings in wild type and mutant zebrafish stand in sharp contrast to previous research and suggest a novel mechanism for rapsyn-AChR interactions. This disparity may stem from the use of model systems that fail to authentically reconstitute neuromuscular synapses. To conclusively determined rapsyn's role in formation and maintenance of the NMJ, I will study function in true neuromuscular junctions using zebrafish as a model vertebrate system. This study may serve as a template for studies of other neuromuscular synapses.

描述（由申请人提供）：我的主要目标是确定 rapsyn 如何指导神经肌肉接头 (NMJ) 处 AChR 密度的增加。当 NMJ 受损时，会对发育和健康产生严重影响。自身免疫性疾病重症肌无力 (MG) 及其遗传对应物先天性肌无力综合征 (CMS) 会导致肌肉无力和疲劳，都是由 NMJ 特定组件（在许多情况下包括 rapsyn）缺陷引起的。迄今为止，rapsyn 的分析仅限于组织培养中的异源表达系统和异位 NMJ。这些研究尚未阐明 rapsyn 的功能，并且只会增加有关其作用方式的争议。野生型和突变斑马鱼的研究结果与之前的研究形成鲜明对比，并提出了 rapsyn-AChR 相互作用的新机制。这种差异可能源于使用的模型系统无法真正重建神经肌肉突触。为了最终确定 rapsyn 在 NMJ 形成和维持中的作用，我将使用斑马鱼作为模型脊椎动物系统来研究真正的神经肌肉接头的功能。这项研究可以作为其他神经肌肉突触研究的模板。